Comparative binding analysis of WGX50 and Alpha-M with APP family proteins APLP1 and APLP2 using structural-dynamics and free energy calculation approaches.

A.D. is a common disease among other neurodegenerative disorders primarily developing due to amyloid-ß (Aß) neurotoxicity derived from the amyloid-ß protein precursor (AßPP). The amyloid precursor-like proteins 1 and 2 (APP1 and APLP2) biochemically behave similarly in many aspects to AßPP. We, therefore, proposed to test WGX-50 and Alpha-M for their interaction mechanism with APLP1 and APLP2 because both these drug candidate compounds previously showed inhibition of Aß aggregation. We employed a comparative atomic investigation on Alpha-M and WGX-50 in complex with novel targets, i.e., APLP1 and APLP2, using biophysical and molecular simulation methods. The docking score was -6.83 kcal mol-1 for Alpha-M-APLP1, -8.41 kcal mol-1 for WGX-50-APLP1, -7.02 kcal mol-1 for Alpha-M-APLP2 and -8.25 kcal mol-1 for the WGX-50-APLP2 complex. Our results also elaborate that in the case of their interaction with both APLP1 and APLP2, the WGX-50 complex exhibits better stability than the APLP1/2-Alpha-M complexes during simulation. Furthermore, WGX50 in both APLP1 and APLP2 stabilized the internal flexibility upon binding in contrast to the Alpha-M complexes. The data showed that the BFE for Alpha-M-APLP1 was calculated to be -27.38 ± 0.93 kcal mol-1, for WGX-50-APLP1 -39.65 ± 0.95 kcal mol-1, for Alpha-M-APLP2 -24.80 ± 0.63 kcal mol-1 while for WGX-50-APLP2 the BFE was -57.16 ± 1.03 kcal mol-1 respectively. These results highlight that APLP2-WGX50 has greater binding energies in all four systems. PCA and FEL analysis further revealed variations in the dynamic behavior of these complexes. Overall, our findings demonstrate that WGX50 potentially acts as a more potent inhibitor for APLP1 and APLP2 than Alpha-M and thus shows the diverse pharmacological potential of WGX50. Due to its stable binding interaction, WGX50 might be a suitable candidate drug compound for targeting these precursors under pathological conditions.

Trypanocidal potential of synthetic p-aminochalcones: In silico and in vitro evaluation.

Chagas disease (CD) is a neglected tropical disease of worldwide health concern, caused by the flagellate protozoan Trypanosoma cruzi (T. cruzi), endemic in Latin America and present in North America and Europe. The WHO recommended drug for CD, benznidazole has low safety profile and several limitations. Therefore, an entity with better therapeutic potential to treat CD is required. Chalcones are an important class of compounds, which have shown antichagasic potential. Thus, the objective of this study was to evaluate the activity of synthetic p-aminochalcones against T. cruzi. Chalcones 1 and 2 were synthesized by Claisen-Schmidt condensation and characterized by both spectroscopic and theoretical methods. Initially, they were submitted to molecular docking simulations using cruzain and trypanothione reductase (TR) enzymes. It was expected to observe the possible interactions of chalcones with the catalytic site and other important regions of these main pharmacological targets of T. cruzi. Their cytotoxicity within host cells were assessed by MTT reduction assay using LLC-MK2 cells, with CC50 = 85.6 ± 9.2 µM and 1115 ± 381.7 µM for chalcones 1 and 2, respectively. These molecules were also tested against epimastigote and trypomastigote life forms of T. cruzi, causing reduction in the number of viable parasites. For the evaluation of the effect on intracellular amastigotes, infected LLC-MK2 cells were incubated with the chalcones for 24 h, causing reduction in the percentage of infected cells and the number of amastigotes/100 cells. Finally, flow cytometry assays were performed for analyzing cell death mechanisms (7-AAD/AxPE labelling), cytoplasmic ROS accumulation (DCFH-DA assay) and mitochondrial transmembrane potential disruption (Rho123 assay). Both chalcones (1 and 2) caused membrane damage, ROS accumulation and mitochondrial depolarization. In conclusion, the synthetic p-aminochalcones presented trypanocidal effect, causing membrane damage and oxidative stress. Their mechanism of action may be related to cruzain and TR inhibition.

Enhancement of paediatric oncology pharmacy practices in a low-middle-income country through teaching and training using the My Child Matters Grant.

The development of a successful oncology pharmacy system includes competency training, cost-efficient procurement, proper storage, preparation and administration of chemotherapy, and appropriate waste disposal. Low-middle-income countries such as Pakistan face several challenges within the realm of oncology pharmacy such as the unavailability of training programmes, resources and financial support, and inconsistencies in the safe handling of cytotoxic drugs. The Indus Hospital and Health Network (IHHN) is among the pioneers of oncology pharmacy practices in Pakistan, with a well-established Oncology Pharmacy Team and chemotherapy preparation in accordance with the United States Pharmacopeia 797 and 800 safety guidelines. The My Child Matters Grant was awarded by the Sanofi Espoir Foundation to the Department of Paediatric Hematology and Oncology at IHHN for holistic improvement in childhood cancer care through teaching, training and capacity building. Partnerships were formed with five public-sector paediatric oncology units nationwide. Initiatives were taken to improve oncology pharmacy practices including teaching and training courses, in-person assessment visits, and mentorship and liaison efforts. Despite prevailing challenges, promising improvements were noted at each centre. However, Pakistan needs to establish a national plan for childhood cancer with the creation of regional organisations for the training and monitoring of oncology pharmacists. Centralisation of pharmacy operations within hospitals is essential to maintain the availability, storage, preparation and administration standards of chemotherapy.

Machine Learning for Dementia Prediction: A Systematic Review and Future Research Directions.

Nowadays, Artificial Intelligence (AI) and machine learning (ML) have successfully provided automated solutions to numerous real-world problems. Healthcare is one of the most important research areas for ML researchers, with the aim of developing automated disease prediction systems. One of the disease detection problems that AI and ML researchers have focused on is dementia detection using ML methods. Numerous automated diagnostic systems based on ML techniques for early prediction of dementia have been proposed in the literature. Few systematic literature reviews (SLR) have been conducted for dementia prediction based on ML techniques in the past. However, these SLR focused on a single type of data modality for the detection of dementia. Hence, the purpose of this study is to conduct a comprehensive evaluation of ML-based automated diagnostic systems considering different types of data modalities such as images, clinical-features, and voice data. We collected the research articles from 2011 to 2022 using the keywords dementia, machine learning, feature selection, data modalities, and automated diagnostic systems. The selected articles were critically analyzed and discussed. It was observed that image data driven ML models yields promising results in terms of dementia prediction compared to other data modalities, i.e., clinical feature-based data and voice data. Furthermore, this SLR highlighted the limitations of the previously proposed automated methods for dementia and presented future directions to overcome these limitations.

Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice.

Acute kidney injury (AKI) causes a decrease in renal function which leads to failure in balancing electrolyte, fluid and acid-base homoeostasis. AKI is a damaging and life-threatening disorder, but it can be managed if identified earlier. This study aimed to investigate the possible nephroprotective effect of Helianthus annuus seeds extract against gentamicin (GM) induced nephrotoxicity in male mice. The control group (0.5 ml normal saline i.p.,), Gentamycin (GM) group (GM 100 mg/kg i.p), silymarin + GM group (silymarin 50 mg/kg and GM 100 mg/kg i.p.,), H. annuus extract (HAE) and GM, group (HAE 250 mg/kg and GM 100 mg/kg i.p), HAE2 + GM group (HAE2; 500 mg/kg and GM 100 mg/kg i.p) and H. annuus oil (HAO) + GM (HAO 2.5 ml/kg and GM 100 mg/kg i.p). Serum creatinine, urea and blood urea nitrogen (BUN) were significantly (P< 0.001) elevated in the GM group compared to the control group. The elevated level of serum creatinine, urea and BUN were decreased significantly (P<0.001) in groups treated with HAE and HAO extracts compared to the GM group. The kidney histopathological study from the GM group showed tubular necrosis, vacuolation and fibrosis. However, the animal that received HAE and HAO showed no tubular necrosis and vacuolation. Only mild inflammation was observed compared to the GM group. In conclusion, the extract caused marked radical scavenger and protected the kidney from oxidative damage of GM. H. annuus seeds contain strong antioxidant compounds, including flavonoids, phenolic acids, tocopherols and minerals, which could be responsible for the current show.

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing. The N proteins reside at CoV RNA synthesis sites known as the replication-transcription complexes (RTCs). The N-terminal of N has RNA-binding domain (N-NTD), capturing the RNA genome while the C-terminal domain (N-CTD) anchors the viral Nsp3, a component of RTCs. Although the structural information has been recently released, the residues involved in contacts between N-CTD with Nsp3 are still unknown. To find the residues involved in interactions between two proteins, three-dimensional structures of both proteins were retrieved and docked using HADDOCK. Residues at N-CTD were detected in interaction with L499, R500, K501, V502, P503, T504, D505, N506, Y507, I508, T509, K529, K530K532, S533 of Nsp3 and N-NTD to synthesize SARS-CoV-2 RNA. The interaction between Nsp3 and CTD of N protein may be a potential drug target. The current study provides information for better understanding the interaction between N protein and Nsp3 that could be a possible target for future inhibitors.

Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases. SUMMARY: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.

Molecular designing, crystal structure determination and in silico screening of copper(II) complexes bearing 8-hydroxyquinoline derivatives as anti-COVID-19.

The pandemic by COVID-19 is hampering everything on the earth including physical and mental health, daily life and global economy. At the moment, there are no defined drugs, while few vaccines are available in the market to combat SARS-CoV-2. Several organic molecules were designed and tested against the virus but they did not show promising activity. In this work we designed two copper complexes from the ligands analogues with chloroquine and hydroxychloroquine. Both the ligands and complexes were well characterized by using various spectroscopic, thermal and X-ray diffraction techniques. Both the complexes as well as ligands were screened through in silico method with the chloroquine and hydroxychloroquine which essentially proved pivotal for successful understanding towards the target protein and their mechanism of action. The results indicated that the balanced hydrophobic and polar groups in the complexes favor their binding in the active site of the viral ADP-ribose-1 monophosphatase enzyme over the parent organic molecules.

Evaluation of catacholase mimicking activity and apoptosis in human colorectal carcinoma cell line by activating mitochondrial pathway of copper(II) complex coupled with 2-(quinolin-8-yloxy)(methyl)benzonitrile and 8-hydroxyquinoline.

To evaluate the cytotoxic potential of metal-based chemotherapeutic candidate towards the colorectal cancer, we have synthesized a new copper(II) complex [Cu(qmbn)(q)(Cl)] (1) (where, qmbn = 2-(quinolin-8-yloxy)(methyl)benzonitrile and q = 8-hydroxyquinoline) and structurally characterized by single crystal X-ray, Powder-XRD, FTIR and thermogravimetric analysis (TGA). The structural analysis reveals that copper(II) ions exist in a distorted square pyramidal (τ = ~0.1), with ligation of a chloride ion, oxygen atom and two nitrogen atoms at equatorial position and one oxygen atom at apical position. The cytotoxicity potential of complex 1 was executed against human colorectal cell lines (HCT116), which showed that 1 induces mitochondrion-mediated apoptotic cell death via activation of the Bax (pro-apoptotic protein) caspases-3 and 9 proteins. Interestingly, complex 1 was found to be a good candidate as electron-transfer catalyst which mimics catacholase with high turnover frequency (kcat = 1.03 × 102 h-1) for the conversion of the model substrate 3,5-di-tertbutylcatechol (3,5-DTBC) to 3,5-di-tertbutylquinone (3,5-DTBQ). Furthermore, molecular docking studies revealed that complex 1 was successfully localized inside the binding pocket of protein kinase (Akt), which validate the mechanism and mode of interaction of 1 that displayed cytotoxic activity experimentally. The obtained outcomes reveal that the complex 1 could be utilized as an encouraging perspective in the development of new therapeutic candidate for colon cancer.

Effect of nursing led discharge instructions on improvement of post discharge care management in heart failure patients at tertiary care hospital of Karachi, Pakistan.

OBJECTIVES: To assess the impact of nursing discharge instructions on post-discharge care management in heart failure patients. METHODS: The quasi- experimental non-randomized study was conducted at the National Institute of Cardiovascular Diseases, Karachi, from January to December 2017, and comprised in-patients suffering from heart failure. They were divided into two equal groups. In the intervention group, discharge instructions and written material was thoroughly given by the nurses other than routine existing instructions for effective post-discharge care management. The control group received discharged instructions under existing routine. Data was analysed using SPSS 21. RESULTS: Of the 80 patients, there were 40(50%) in each group with no significant difference in terms of age, gender and education (p>0.05 each). Regarding awareness and control of the disease, adherence with medication and proper management of their illness, the intervention group had higher level of competency than the control group (p=0.001). CONCLUSIONS: Provision of nursing interventions to educate the patient of heart failure during hospitalisation, on discharge, follow-up day and continuous guidance on telephone significantly improved the post-discharge care management of the patients.

Helix-Switch Enables C99 Dimer Transition between the Multiple Conformations.

C99 is the immediate precursor of amyloid-ß (Aß) and therefore is a central intermediate in the pathway that is believed to result in Alzheimer's disease (AD). Recent studies have shown that C99 dimerization changes the Aß ratio, but the mechanism remains unclear. Previous studies of the C99 dimer have produced controversial structure models. To address these questions, we investigated C99 dimerization using molecular dynamics (MD) simulations. A helix-switch model was revealed in the formation and transition of the C99 dimer, and six types of conformations were identified. The different conformations show differential exposures of γ-cleavage sites and insertion depths in the bilayer, which may modulate γ-cleavage of C99 and lead to different Aß levels. Our results redefine C99 dimerization, provide a framework to mediate the current controversial results, and give insights into the understanding of the relationship between C99 dimerization and Aß formation.

rs2651899 variant is associated with risk for migraine without aura from North Indian population.

Recently a GWAS study had identified 38 genomic variants commonly found in humans that influence migraine risk. For further replicate these findings, we selected two SNPs; rs2651899 on chromosome 1p36.32 in PRDM16 gene and rs10166942 on chromosome 2q37.1 close to TRPM8 gene for their associations with migraine in the North Indian population as much work has not been done on these variants before from this population. In this case-control association study, 300 unrelated subjects, including 150 migraineurs (43 migraine with aura and 107 migraine without aura) and 150 healthy controls were selected to collect genomic DNA. Polymerase chain reaction and restriction-fragment-length polymorphism methods were performed for genotyping of these variants. Univariate and multivariate analyses were done to find the association of different genotypes and alleles of these SNPs with migraine and its subgroups. We found a statistically significant difference in migraineurs with control for PRDM16 rs2651899 polymorphism at genotypic (p < 0.05), allelic (p = 0.022; OR 1.462; 95% CI 1.058-2.022) and for dominant model (p = 0.011; OR 1.957; 95% CI 1.169-3.276). A similar trend was observed both on subgroup and gender analysis in migraine without aura (MO) and females respectively for rs2651899 variant. For the other SNP (rs10166942), statistically non-significant differences were reported in the allelic/genotypic frequencies between migraineurs and controls as p > 0.05. However, on subgroup analysis we found statistically significant differences at genotypic (p < 0.05) and dominant models in migraine with aura (MA) and in males with that of entire controls. But no significant association was found at allelic level in both subgroup and gender analysis for rs10166942. This research study showed that rs2651899 is a potential genetic marker for migraine susceptibility in MO and female subgroup at both genotypic and allelic level in the North Indian population and found that rs10166942 variant may be a potential marker for MA and male subgroup. Further work with large sample size is required for these SNPs to understand their functional mechanisms and to strengthen our results.

Predictors of an increased length of stay following Total Knee Arthroplasty - Survey Report.

OBJECTIVE: To find various preoperative, intraoperative and postoperative factors that predict an increased length of stay in patients following total knee arthroplasty. METHODS: The retrospective cohort study was conducted at the Aga Khan University Hospital, Karachi, and comprised record of patients regardless of gender, co-morbids and age who had undergone a unilateral or bilateral total knee arthroplasty between January 2007 and December 2015. An increased length of stay was defined as ≥75th centile (≥11 days). RESULTS: Of the 577 patients, 448(77.6%) were women. Overall, 311(53.9%) patients were aged 56-70 years. Of the total, 100(17.3%) patients stayed for at least 11 days. There was a weak but positive correlation between increasing body mass index and increased length of stay (p=0.017). Following adjusted-multivariate logistic regression analysis, the most significant predictors contributing to an increased length of stay were bilateral knee surgery, postoperative transfusion and postoperative special care unit stay (p<0.05 each). CONCLUSIONS: Bilateral total knee arthroplasty, postoperative transfusion and postoperative special care unit stay were found to be associated with an increased length of stay.

Low cost reconstructive options after musculoskeletal tumour resection in developing countries. Affordable, effective and durable alternatives.

Over the last two, three decades, the overall survival rates for non-metastatic malignant tumours of the bone have dramatically improved. This has become possible due to the recent advances and multidisciplinary approach towards these diseases, specifically the advent of multi-agent chemotherapy and radiotherapy. Limb salvage has now become the norm in the treatment of musculoskeletal tumours without compromising on the overall survival and recurrence of the disease. In the era of metal, prosthetic reconstruction has become the standard procedure specifically in the large tumours which involve the joints as this method of reconstruction helps in joint mobility and early weight-bearing. Considering the costs and resource constraints, multiple cost-effective, stable, durable reconstruction options have evolved over the last decade and these have also shown favourable func tional outcomes without compromising on the amount of resection and risk of local recurrence. The current literature review was planned to discuss various cost-effective, durable reconstructive options and their advantages and disadvantages. These include Van ness rotationplasty, allograft, autograft, devitalised tumour bone and Masqueletor induced membrane technique . .

Influence of dietary practices on Blood pressure: comparison between house wives and employed women.

OBJECTIVE: To compare the occurrence and to determine relationship of dietary practices with hypertension between housewives and working women.. METHODS: The cross-sectional study was conducted at Karachi University and Dow University of Health Sciences, Karachi, from January to April 2015, and comprised working women and housewives who were enrolled using convenient sampling. Data was collected on consumption of fruits, vegetables, poultry/fish and fast food. Blood pressure and body mass index were noted and interpreted according to World Health Organisation classification for Asian population. Normal reference range of blood pressure was taken as Systolic100-120mmHg, Diastolic 60-90 mmHg, and mean value as 120/80mmHg. Data analysis was done using SPSS17. RESULTS: There were 600 subjects; with 300(50%) housewives and as many working women. Mean age of housewives was 35.56}7.53 years, and that of employed women 35.44}6.65 years. Among the housewives, 96(32%) had normal blood pressure while the corresponding number in the other group was 198(66%) (p<0.001). In terms of relationship body mass index with hypertension, out of the 204(68%) hypertensive housewives, 90(44.1%) were overweight, and of the 102 hypertensive working women, 40(39.23%) had normal weight range. Most housewives reported a sedentary lifestyle as opposed to working women (p<0.001).. CONCLUSIONS: Being a housewife was in itself found to be a contributing factor in hypertensive disorders.

Recent Trend in Specialty Choices of Medical Students and House Officers from Public Sector Medical Universities, Karachi.

OBJECTIVE: To determine career choices of medical students of public-sector medical universities and factors affecting their career choices. METHODS: The cross-sectional study was conducted at Dow University of Health Sciences and Jinnah Sindh Medical University, Karachi, from May 2015 to May 2016, and comprised 4th and 5th year medical students and house officers. A self-administrated structured questionnaire was used to collect data which was entered and analysed using SPSS 20. RESULTS: Of the 445 Subjects, 314(70.6%) were females. There were 206(46.3%) 4th year students, 194(43.6%) were from the 5th year and 45(10%) were house officers. Top 15 medical specialties were ranked according to the respondents' top three choices. Internal medicine 67(15.1%), cardiology 47(10.6%), paediatrics 46(10.3%) and general surgery 40(9.0%) were the four highest ranked specialties. Overall, 377(84.7%) subjects said prestige in working in that field was the reason of their respective choices. CONCLUSIONS: Medical students chose a wider range of specialties and stated varying factors affecting their choices.

NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients.

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m2 of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1-3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

Association of MTHFR gene polymorphisms with migraine in North Indian population.

Polymorphisms in MTHFR gene are mostly associated with increased levels of homocysteine in the absence of dietary folate and are a risk factor for complex neurovascular diseases like migraine. The aim of present case-control study was to determine the association between MTHFR gene polymorphisms (C667T; rs 1801133, A1298C; rs 1801131) with migraine susceptibility. In total, 100 patients with migraine (23with MA and 77 with MO) and age-sex matched 100 healthy controls were included in this study from OPD of ESIC Medical College & Hospital, Faridabad. Genotyping was done by PCR-RFLP method. Genotypic and allelic frequencies were compared by SPSS 24 version. Genotypic results indicated a non-significant increase in frequencies of CT and TT in C667T SNP in migraine patients with control (52 and 10% vs. 42 and 7%: p > 0.05), but CC genotype in A1298C was found to be a risk factor in migraine patients than controls (30 vs. 17% respectively: p < 0.05). On comparing migraine subclasses, migraine with aura (MA) and without aura (MO) with control groups, the present study suggests that in MTHFR polymorphisms, the prevalence of 677CT genotype and T allele in C667T SNP influences susceptibility to MA (p < 0.05) but not to MO. Meanwhile, CC genotype in A1298C SNP could be a risk factor for migraine patients without aura (p < 0.05).

Frequency of bacterial contamination in platelet concentrates in a tertiary care cardiac hospital in Rawalpindi, Pakistan.

Bacterial contamination of platelets concentrates (PCs) can result in transfusion transmissible infection. Storage temperature for platelets provides favourable environment for the bacterial growth. This study was conducted at Rawalpindi Institute of Cardiology, Rawalpindi, Pakistan from May, 2016 to July 2016. A total of 200 (48 hours stored) whole blood derived PCs collected were selected for the study. Sample were inoculated into Oxoid Signal blood culture bottles and incubated at 36±1°C for 07 days. Signal culture bottle with positive signals and visual appearance of turbidity were sub-cultured. Bacterial growth identification was carried out by standard reference methods. Out of 200 platelets concentrates, 63 suspected turbid and 02 with positive signal culture device were sub-cultured and identified. Staphylococcus aureus was identified in 02 bottles. The overall frequency of bacterial contamination in PCs was found to be 1%. The frequency of bacterial contamination in PCs found is very high as compared to developed counties. There is need of strict adherence to standard protocols for the prevention, early detection, and reporting of bacterial contamination in the PCs in Pakistan.

Matrix metalloproteinases: their functional role in lung cancer.

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis.